VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain
Zheng Gang Zhang, … , Nicholas van Bruggen, Michael Chopp
Zheng Gang Zhang, … , Nicholas van Bruggen, Michael Chopp
Published October 1, 2000
Citation Information: J Clin Invest. 2000;106(7):829-838. https://doi.org/10.1172/JCI9369.
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VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain

Abstract

VEGF is a secreted mitogen associated with angiogenesis and is also a potent vascular permeability factor. The biological role of VEGF in the ischemic brain remains unknown. This study was undertaken to investigate whether VEGF enhances cerebral microvascular perfusion and increases blood-brain barrier (BBB) leakage in the ischemic brain. Using magnetic resonance imaging (MRI), three-dimensional laser-scanning confocal microscope, and functional neurological tests, we measured the effects of administrating recombinant human VEGF165 (rhVEGF165) on angiogenesis, functional neurological outcome, and BBB leakage in a rat model of focal cerebral embolic ischemia. Late (48 hours) administration of rhVEGF165 to the ischemic rats enhanced angiogenesis in the ischemic penumbra and significantly improved neurological recovery. However, early postischemic (1 hour) administration of rhVEGF165 to ischemic rats significantly increased BBB leakage, hemorrhagic transformation, and ischemic lesions. Administration of rhVEGF165 to ischemic rats did not change BBB leakage and cerebral plasma perfusion in the contralateral hemisphere. Our results indicate that VEGF can markedly enhance angiogenesis in the ischemic brain and reduce neurological deficits during stroke recovery and that inhibition of VEGF at the acute stage of stroke may reduce the BBB permeability and the risk of hemorrhagic transformation after focal cerebral ischemia.

Authors

Zheng Gang Zhang, Li Zhang, Quan Jiang, Ruilan Zhang, Kenneth Davies, Cecylia Powers, Nicholas van Bruggen, Michael Chopp

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Late (48 hours) administration of rhVEGF165 to ischemic rats did not res...
Late (48 hours) administration of rhVEGF165 to ischemic rats did not result in increases in BBB leakage. Postcontrast images (b) obtained at 30 minutes after injection of the Gd-DTPA agent did not show an increase in areas of hyperintensity compared with the precontrast image (a) in a rat treated with rhVEGF165 at 48 hours of MCA occlusion. Non- and low cerebral microvascular plasma perfusion was detected in the ipsilateral MCA-supplied territory on a composite image of LSCM (80 μm thickness) (c). However, extravasation of Evans blue and FITC-dextran was not detected (c). Images of LSCM were obtained immediately after the last Gd-DTPA–enhanced MRI measurements.